Glial activation in white matter following ischemia in the neonatal P7 rat brain

Biran, Valérie; Joly, Luc‐Marie; Héron, Anne; Vernet, Agnès; Vega, Carolina; Mariani, Jean; Renolleau, Sylvain; Charriaut‐Marlangue, Christiane

doi:10.1016/j.expneurol.2006.01.037

Cited by 75 publications

(52 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In this regard, studies of astroglial cell death after different types of acute injuries such as traumatic brain injury (Beer et al, 2000;Newcomb et al, 1999) and ischemia/ excitotoxicity (Biran et al, 2006;Dihne et al, 2001), have shown that apoptosis occurs only in few astrocytes, in agreement with our findings in the injured neonatal brain. Alternatively, non-apoptotic roles of caspase-3 need to be considered.…”

Section: Discussionsupporting

confidence: 91%

Caspase‐3 activation in astrocytes following postnatal excitotoxic damage correlates with cytoskeletal remodeling but not with cell death or proliferation

Acarín¹,

Villapol²,

Faiz³

et al. 2007

Glia

View full text Add to dashboard Cite

Caspase-3 has classically been defined as the main executioner of programmed cell death. However, recent data supports the participation of this protease in non-apoptotic cellular events including cell proliferation, cell cycle regulation, and cellular differentiation. In this study, astroglial cleavage of caspase-3 was analyzed following excitotoxic damage in postnatal rats to determine if its presence is associated with apoptotic cell death, cell proliferation, or cytoskeletal remodeling. A well-characterized in vivo model of excitotoxicity was studied, where damage was induced by intracortical injection of N-methyl-D-asparate (NMDA) in postnatal day 9 rats. Our results demonstrate that cleaved caspase-3 was mainly observed in the nucleus of activated astrocytes in the lesioned hemisphere as early as 4 h postlesion and persisted until the glial scar was formed at 7-14 days, and it was not associated with TUNEL labeling. Caspase-3 enzymatic activity was detected at 10 h and 1 day postlesion in astrocytes, and co-localized with caspasecleaved fragments of glial fibrillary acidic protein (CCP-GFAP). However, at longer survival times, when astroglial hypertrophy was observed, astroglial caspase-3 did not generally correlate with GFAP cleavage, but instead was associated with de novo expression of vimentin. Moreover, astroglial caspase-3 cleavage was not associated with BrdU incorporation. These results provide further evidence for a nontraditional role of caspases in cellular function that is independent of cell death and suggest that caspase activation is important for astroglial cytoskeleton remodeling following cellular injury. V V C 2007 Wiley-Liss, Inc.

show abstract

Section: Discussionsupporting

confidence: 91%

Caspase‐3 activation in astrocytes following postnatal excitotoxic damage correlates with cytoskeletal remodeling but not with cell death or proliferation

Acarín¹,

Villapol²,

Faiz³

et al. 2007

Glia

View full text Add to dashboard Cite

show abstract

“…We next analyzed the white matter underlying cortical stroke in both the cingulum and external capsule (Fig. 3), where cell damage has been previously reported (19). Melatonin treatment was associated with a significant decrease in the density of TL-positive cells in the cingulum (by 30%, p Ͻ 0.05) and external capsule (by 40%, p Ͻ 0.05) when compared with vehicle-treated animals ( Table 1).…”

Section: Resultsmentioning

confidence: 99%

“…We previously developed a neonatal model of stroke in 7-d-old (P7) rat characterized by apoptotic cell death (16,17), inflammatory responses (18,19), and oxidative stress (20). In addition to cerebral infarct, this model induced glial activation in underlying white matter including persistent activation of microglia and astrogliosis (19,21). As the presence of activated microglia is known to impair the oligodendroglial lineage, we hypothesized that melatonin could be used as an effective neuroprotectant in this stroke model.…”

mentioning

confidence: 99%

“…Melatonin was shown to have a potent protective effect in several models of developing white matter damage, by not only promoting oligodendroglial maturation and myelination repair but also decreasing astrogliosis and microglial activation (12)(13)(14)(15). We previously developed a neonatal model of stroke in 7-d-old (P7) rat characterized by apoptotic cell death (16,17), inflammatory responses (18,19), and oxidative stress (20). In addition to cerebral infarct, this model induced glial activation in underlying white matter including persistent activation of microglia and astrogliosis (19,21).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Melatonin Promotes Myelination by Decreasing White Matter Inflammation After Neonatal Stroke

et al. 2011

Self Cite

View full text Add to dashboard Cite

Melatonin demonstrates neuroprotective properties in adult models of cerebral ischemia, acting as a potent antioxidant and anti-inflammatory agent. We investigated the effect of melatonin in a 7-d-old rat model of ischemia-reperfusion, leading to both cortical infarct and injury in the underlying white matter observed using MRI and immunohistochemistry. Melatonin was given i.p. as either a single dose before ischemia or a double-dose regimen, combining one before ischemia and one 24 h after reperfusion. At 48 h after injury, neither a significant reduction in cortical infarct volume nor a variation in the number of TUNEL-and nitrotyrosine-positive cells within the ipsilateral lesion was observed in melatonin-treated animals compared with controls. However, a decrease in the density of tomato lectin-positive cells after melatonin treatment was found in the white matter underlying cortical lesion. Furthermore, we showed a marked increase in the myelin basic protein-immunoreactivity in the cingulum and in the density of mature oligodendrocytes (APCimmunoreactive) in both the ipsilateral cingulum and external capsule. These results suggest that melatonin is not able to reduce cortical infarct volume in a neonatal stroke model but strongly reduces inflammation and promotes subsequent myelination in the white matter. (Pediatr Res 69: 51-55, 2011) N eonatal hypoxia-ischemia is an important cause of neonatal brain injury, resulting in cerebral palsy, learning disabilities, visual field deficits, and epilepsy (1). In addition to global cerebral ischemia arising from systemic asphyxia, recent data suggest a higher incidence of focal ischemiareperfusion leading to stroke in near-term neonates (2,3). Mechanisms of arterial ischemic injury without the confounding effect of hypoxia are not fully understood. Although therapeutic hypothermia has recently demonstrated a benefit by decreasing brain tissue injury in infants with hypoxicischemic encephalopathy (4,5), very little is known regarding potential neuroprotective strategies after neonatal stroke.Melatonin, an indoleamine, is synthesized and secreted from the pineal gland relative to the circadian rhythms. Melatonin readily crosses the blood-brain barrier, and after exogenous administration, it is found in high concentrations in the brain. It was demonstrated that melatonin has neuroprotective effects through either antiapoptotic (6) or antioxidant effects (7,8) or by decreasing the excitotoxic cascade (9). Melatonin has demonstrated neuroprotective properties in adult models of cerebral ischemia, acting as a potent antioxidant and antiinflammatory agent (10,11). Melatonin was shown to have a potent protective effect in several models of developing white matter damage, by not only promoting oligodendroglial maturation and myelination repair but also decreasing astrogliosis and microglial activation (12-15). We previously developed a neonatal model of stroke in 7-d-old (P7) rat characterized by apoptotic cell death (16,17), inflammatory responses (18,19), and oxid...

show abstract

“…Coronal section, 5 μm-thick, were used for staining, immunohistochemistry (IHC) and immunofluorescence (IF), as previously described by Girard et al (2009). Primary antibodies (Abs) included Abs directed against: glial fibrillary acid protein (GFAP; 1:500, Chemicon, ON, Canada; Ferrucci et al, 2010;Girard et al, 2009), ionized calcium binding adapter molecule 1 (Iba-1; 1:500, Wako Chemicals, VA, US; Faustino et al, 2011;Girard et al, 2009), proliferating cell nuclear antigen (PCNA; 1:500, Santa Cruz Biotechnology, CA, US; Girard et al, 2010b), myelin basic protein (MBP; 1:500, Chemicon, ON, Canada; Biran et al, 2006;Girard et al, 2009), doublecortin (DCX, 1:500, Abcam MA, US; Geoghegan and Carter, 2008) and neuronal nuclei (NeuN, 1:100, Millipore, MA, US; Liew et al, 2012). After washing, sections were incubated with the appropriate secondary Ab: anti-mouse-HRP (1:100, Santa Cruz Biotechnology, CA, US) or anti-rabbit-HRP (1:100, Serotec, NC, US) for IHC, and anti-mouse, anti-chicken or antirabbit alexa fluoconjugated (1:500, Invitrogen, ON, Canada) for IF.…”

Section: Brain Histological Analysismentioning

confidence: 99%

Postnatal administration of IL-1Ra exerts neuroprotective effects following perinatal inflammation and/or hypoxic-ischemic injuries

Girard¹,

Sébire²,

Brochu³

et al. 2012

Brain, Behavior, and Immunity

View full text Add to dashboard Cite

New therapeutic strategies are needed to protect neonates, especially premature newborns, against brain injury and associated neurobehavioral deficits. The role of pro-inflammatory cytokines, especially IL-1β, in the pathophysiological pathway leading to neonatal brain damage is increasingly recognized and represents an attractive therapeutic target. We investigated the therapeutic potential of postnatal systemic administration of the interleukin (IL)-1 receptor antagonist (IL-1Ra) in an animal model of perinatal brain injury using the insults most common to human neonates, i.e. prenatal exposure to inflammation and/or postnatal hypoxia-ischaemia (HI). We found that postnatal administration of IL-1Ra preserved motor function and exploratory behavior after either prenatal exposure to inflammatory agent lipopolysaccharide (LPS) or postnatal HI insult. The deleterious effect of combined prenatal LPS and postnatal HI on brain development was also alleviated by administration of IL-1Ra, as seen by the protected neural stem cell population, prevention of myelin loss in the internal capsule, decreased gliosis, and decreased neurobehavioral impairment. This study showed the distinct pattern of functional deficits induced by prenatal inflammation as compared to postnatal HI and the therapeutic potential of IL-1Ra administration against neonatal brain injury. Furthermore, our results highlight the potential for postnatal treatment of prenatal inflammatory stressors.

show abstract

Glial activation in white matter following ischemia in the neonatal P7 rat brain

Cited by 75 publications

References 45 publications

Caspase‐3 activation in astrocytes following postnatal excitotoxic damage correlates with cytoskeletal remodeling but not with cell death or proliferation

Caspase‐3 activation in astrocytes following postnatal excitotoxic damage correlates with cytoskeletal remodeling but not with cell death or proliferation

Melatonin Promotes Myelination by Decreasing White Matter Inflammation After Neonatal Stroke

Postnatal administration of IL-1Ra exerts neuroprotective effects following perinatal inflammation and/or hypoxic-ischemic injuries

Contact Info

Product

Resources

About